Joint Hypermobility Syndrome (JHS), also referred to as hypermobile Ehlers-Danlos Syndrome (hEDS), is increasingly recognised as a significant contributor to gynaecological, pelvic floor and lower urinary tract symptoms. This review aims to highlight the current evidence on the relationship between JHS and key urogynaecological conditions, with particular attention to recent developments in epidemiology, clinical presentation, and management. Emerging research demonstrates a strong association between JHS and pelvic organ prolapse (POP), with meta-analytic data showing more than a twofold increased risk. Large cohort studies highlight substantial symptom burden, including high rates of stress and urgency incontinence, bladder pain, pelvic floor dysfunction and sexual difficulties. Recent work also reveals distinct challenges in perioperative care, such as dysautonomia-related anaesthetic risks, tissue fragility, impaired wound healing and higher rates of surgical complications in some series. Studies document higher prevalence of urinary incontinence, bladder diverticula, recurrent urinary infections and voiding dysfunction linked to increased bladder capacity and elevated residual volumes. Women with JHS experience a wide and often severe spectrum of urogynaecological symptoms that significantly affect quality of life. Although management generally mirrors standard care pathways, the unique connective-tissue and systemic features of JHS necessitate tailored assessment and multidisciplinary involvement. Further high-quality research is required to develop specific management algorithms and clarify the role of conservative versus surgical treatments in this complex clinical population.

: Postural orthostatic tachycardia syndrome (POTS) includes multiple symptoms and comorbid conditions. Assessment for less recognized symptoms and conditions was performed through a telemedicine-only clinic for adolescent and young adult patients with POTS. : A retrospective review of records was performed for information obtained during clinical care. Patients up through the age of 23 years were evaluated, either diagnosing or confirming a diagnosis of POTS, and identifying other symptoms and diagnoses. These data were evaluated for differences, including by sex and presence or absence of joint hypermobility. : In total, 277 patients met the inclusion criteria. The median age was 16.8 years (IQR 15.2-19.1); 88.1% were female. Suspected mast cell activation syndrome occurred in 70% of patients. Joint hypermobility was found in 78.3% of patients; female patients were more affected (80.3% versus 63.6%); 57.0% had both suspected MCAS and joint hypermobility. Migraine was seen in 51.6% of patients; 57.4% had tension-type headache. Females appeared more likely to have tension headache or both types of headache together, while males seemed more likely to have migraine. Joint hypermobility did not influence headache presence or absence. A history of head trauma/concussion was reported in 39.7% of patients, with 14.4% having vestibular symptoms and 4% having convergence disorder. Without head trauma/concussion, 23.8% of patients reported vestibular symptoms, convergence disorder, or both. : We report previously unrecognized or poorly described symptoms and conditions accompanying POTS. Recognition of these symptoms and conditions in patients with POTS can allow for more complete evaluation and management of debilitating factors and may give insights into underlying pathophysiologies leading to POTS.

The objective of this study was to investigate the potential association between the use of calcitonin gene-related peptide (CGRP) antagonists and the reporting of cardiac adverse events (cAEs) by analyzing data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). CGRP antagonists are a novel class of effective treatments for migraine. However, given CGRP's crucial role as a potent vasodilator, concerns about the cardiac safety of its long-term blockade persist. This study aimed to assess real-world post-marketing safety signals for this drug class. FAERS data from Q1 2018 to Q2 2025 were analyzed. CGRP antagonists included monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) and small-molecule receptor antagonists (rimegepant, ubrogepant, atogepant). Disproportionality analyses were conducted using the reporting odds ratio (ROR) and information component (IC). The impact of age, sex, and weight on cAE was assessed. Time-to-onset analyses were also carried out. A total of 1806 cAE reports associated with CGRP antagonists were identified. Palpitations emerged as a consistent signal across all seven agents, suggesting a class effect. Monoclonal antibodies, particularly erenumab and fremanezumab, exhibited a broader spectrum of cAE signals, including coronary artery dissection, Prinzmetal angina, and postural orthostatic tachycardia syndrome. The results showed higher body weight was significantly associated with the cAE signal of disproportionate reporting (SDR) of erenumab (odds ratio [OR] 1.48, 95% CI 1.02-2.11, P = 0.034). Meanwhile, male sex was significantly associated with the cAE SDR of galcanezumab (OR 2.41, 95% CI 1.25-4.40, P = 0.006). Time-to-onset analyses indicated that most cAEs followed an early failure pattern, with the highest reporting intensity shortly after treatment initiation. Using FAERS, this pharmacovigilance study detected signals of disproportionate reporting of cardiac adverse events for most CGRP antagonists. These results are hypothesis-generating and reflect reporting patterns rather than incidence or relative risk; therefore, they should not be interpreted as evidence of causality or as patient-level cAE risk factors. Continued post-marketing surveillance and confirmatory pharmacoepidemiologic studies in well-defined populations are warranted.  CLINICAL TRIAL NUMBER: Not applicable.

Postural orthostatic tachycardia syndrome (POTS), characterized by a rise in heart rate of at least 30 beats per minute from supine to standing position without accompanying orthostatic hypotension, is one of the most common autonomic disorders with disabling cardiovascular and neurologic manifestations. Hormonal influence has been long recognized by the disorder predominantly affecting women of reproductive age, with frequent onset around menarche, exacerbation of symptoms before or during menses, and pregnancy being one of POTS triggers. Hormone replacement therapy (HRT) and menopause in women with POTS have not been studied, but issues surrounding HRT are highly relevant as women with POTS transition from reproductive age to menopause. Given a rising prevalence of POTS due to post-COVID onset and the US Food and Drug Administration recently removing the black box warning on estrogen-containing HRT formulations, informed decisions and risk assessments regarding HRT use in women with POTS are warranted. In this narrative review, existing studies on hormones and POTS and its common comorbidities are reviewed, and key points in decision-making on the use of HRT in women with POTS are discussed. In summary, for women with significant menopausal symptoms and/or exacerbation of POTS during the peri- or postmenopausal period, using some forms of HRT for treatment of menopausal symptoms may be considered, accounting for comorbidities, cardiovascular risk and other factors. Vaginal estrogen appears to be safe for most women while transdermal estrogen and micronized progesterone can be utilized for significant menopausal symptoms, although outcomes of their long-term use are unknown.

Patients with Postural Orthostatic Tachycardia Syndrome (POTS) and Orthostatic Intolerance (OI) commonly present with symptoms suggestive of Pelvic Venous Disorders (PeVD). The presence of PeVD may contribute to orthostatic symptoms in these patients due to venous obstruction with stasis and pooling. Iliac vein compression, a PeVD, has historically been treated with iliac venous stenting. The authors hypothesize that patients with POTS frequently have findings of PeVD, that venous outflow obstruction from iliac vein compression exacerbates POTS/OI symptomatology, and that treating PeVD improves POTS/OI symptoms. This paper reports results from two studies at two different institutions with a partially overlapping patient population. The first was a retrospective cross-sectional observational study of patients with POTS/OI who presented to Emory University Cardiology (Atlanta, GA, USA) from October 2019 to June 2023. We aimed to evaluate the prevalence of concurrent POTS/OI and PeVD using screening pelvic venous ultrasound, MR and/or CT, compared to venogram with intravascular ultrasound (IVUS). We secondarily evaluated the efficacy of each imaging modality in screening accuracy for PeVD. The second study was a retrospective review of medical records for 271 female patients with POTS/OI who received treatment of PeVD with iliac vein stenting from June 2019 to November 2024 at Minimally Invasive Procedure Specialists (Highlands Ranch, CO). The primary objective of this study was to explore quality of life (QoL) outcomes in female patients with POTS/OI before and after treatment. The secondary objective was to record the prevalence of associated pelvic pain, systemic symptoms, and response to therapy in this population. In the first cohort, 129 patients (84% cis female) with a diagnosis of POTS/OI and symptoms of PeVD were assessed by standard imaging for venous pathology. 107 patients (83%) had confirmed pelvic venous compression (iliac vein, renal vein, or both) or pelvic venous congestion on imaging with at least one screening modality. All screening modalities were relatively insensitive in detecting iliac venous compression compared with venography and IVUS. In the second cohort, following iliac vein stenting, significant improvements were seen in Orthostatic Hypotension Questionnaire (OHQ) composite scores at three months (p < 0·001) and at 12 months (p < 0·001). The OHQ Symptom Assessment (OHSA) and Daily Activities Scale (OHDAS) subscores, International Pelvic Pain Society (IPPS) score, Pelvic Congestion Syndrome (PCS) score, Pelvic Pain and Urgency/Frequency Symptom Scale (PUF) score, and Ancillary symptom score all demonstrated statistically significant decreases at three months that persisted at 12 months (all p < 0·001) as well. The high prevalence of PeVD in POTS/OI patients suggests an association between the two diagnoses. In the absence of expert clinical review, screening with US, CT, and MR may not be sufficient to rule out PeVD. Significant improvements were seen in QoL in patients with POTS/OI and PeVD who underwent iliac vein stenting. These results call for additional trials to examine the clinical and hemodynamic effects of venous stenting on POTS/OI symptomatology and associated systemic symptoms, including pelvic pain. These studies received no funding.

Postural Orthostatic Tachycardia Syndrome (POTS) and Neurally-Mediated Hypotension (NMH) are heterogeneous syndromes characterized by dysautonomia and multisystem symptoms. Mast cell activation, often manifesting as hives, has been proposed as a contributing mechanism, but its prevalence and clinical relevance in POTS and NMH are poorly defined. Patients from the Johns Hopkins POTS Clinic completed surveys assessing hives frequency and symptom burden using the Malmö POTS, the Composite Autonomic Symptom Score (COMPASS)-31, and a pain questionnaire. Associations between hives and clinical features were evaluated among patients with confirmed POTS, NMH, or clinically diagnosed orthostatic intolerance. Among 188 respondents, 80 (42.6%) reported hives sometimes and 33 (17.6%) reported hives often or always. Increasing hives frequency was associated with higher Malmö POTS scores and greater autonomic symptom burden across multiple COMPASS-31 subdomains, including gastrointestinal, bladder, and vasomotor symptoms (all  < 0.05). Hives was also associated with pain (OR 3.47, 95% CI 1.54-7.77,  = 0.002) and tingling (OR 5.73, CI 2.15-15.26,  < 0.001), but not orthostatic symptoms. These associations persisted after multivariable adjustment. Hives are common in orthostatic intolerance syndromes and are associated with increased symptom burden. Future studies are needed to clarify the role of mast cell activation and evaluate mast cell-targeted therapies.

Postural orthostatic tachycardia syndrome (POTS) is a common autonomic disorder of heterogeneous pathophysiology involving relative sympathetic overactivity and/or parasympathetic hypofunction. Postural orthostatic tachycardia syndrome is characterized by exaggerated postural tachycardia in the absence of orthostatic hypotension, in conjunction with orthostatic intolerance and other cardiovascular and neurologic features. We report a 30-year-old woman with POTS who experienced significant improvement with pyridostigmine. The whole genome sequencing demonstrated four single nucleotide polymorphisms-AchE, BChE, PEMT, and CHDH-variants involved in acetylcholine processing that may have led to acetylcholine deficiency and resultant parasympathetic hypofunction with relative sympathetic hyperactivity in this patient. Her Composite Autonomic Symptom Score-31 (COMPASS-31) after initiation of pyridostigmine decreased from 56.15 pre-treatment to 32 post-treatment, which indicated a 43% improvement in autonomic symptom burden, while her daily step count increased from an average of 4000 steps pre- to 7500 steps post-treatment with pyridostigmine. We hypothesize that genetic variants in acetylcholine processing may result in acetylcholine deficiency state and may represent one of many pathophysiologic mechanisms of POTS. Whole genome sequencing and validated genetic tests for these and other genetic variants may be valuable diagnostic tools in delineating specific pathophysiology, POTS phenotypes, and personalized treatment approaches.

Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most common type of inherited connective tissue disorder, often presenting with chronic widespread myofascial pain, autonomic dysfunction, soft-tissue fragility, and psychiatric comorbidities. Pain is often multifactorial and refractory to conventional therapies. We describe a young adult with longstanding hypermobility, recurrent subluxations, chronic periscapular pain, migrainous headaches, and dysautonomia who achieved marked clinical improvement with lidocaine-based therapies, including trigger-point injections (TPIs) and scheduled intravenous lidocaine infusion. TPIs provided more than 50% relief of the myofascial pain for over one month, which is significantly longer than the typical duration of conservative treatments. A lidocaine infusion was subsequently administered to provide extended and more widespread pain relief, resulting in a favorable clinical outcome. This case illustrates the value of lidocaine as part of a multimodal strategy in managing complex hypermobility-related pain syndromes.

The association between blood pressure variability (BPV) or heart rate variability (HRV) and the baroreflex is well established. However, the role of the vestibular-autonomic reflex in regulating BP and HR stability has primarily been explored only in experimental studies. We aimed to delineate the association of BPV and HRV with otolith function in postural orthostatic tachycardia syndrome (POTS). We retrospectively analyzed data from consecutive patients with POTS recruited between April 2021 and April 2025 at a tertiary referral-based hospital in South Korea. All patients underwent a head-up tilt table test using a Finometer device and cervical (cVEMP) and ocular vestibular evoked-myogenic potentials (oVEMP). The Finometer data were analyzed using a power spectral analysis. The Finometer, cVEMP, and oVEMP data were compared with those of 32 age- and sex-matched healthy participants. A total of 47 patients with POTS (mean age standard deviation [SD] = 33 10 years; 30 female patients) and 32 age- and sex-matched healthy participants were included for analysis. The n1-p1 amplitude of oVEMP was larger in patients with POTS than in healthy participants (p = 0.002). p13 latency was negatively correlated with the SD of heart rate in the supine position in patients with POTS (p = 0.001), a trend not observed in healthy participants. The n1-p1 amplitude (odds ratio [95% confidence interval] = 1.27 [1.08-1.49], p = 0.004) and root mean square of successive differences (RMSSD) during tilting (0.82 [0.72-0.93], p = 0.001) were associated with POTS after adjusting for other covariates. Otolithic function may play a role in accentuating BPV and HRV in POTS by contributing to enhanced sympathetic outflow.

Despite the central role of exercise in treating postural orthostatic tachycardia syndrome (POTS) there have been no studies on the subjective experience of exercise interventions and/or recommendations among this patient population. The purpose of this mixed-methods study was to provide greater understanding of the perceived barriers, preferences, perceptions of exercise, and experiences implementing exercise recommendations for adults with POTS in order to optimize treatment recommendations and intervention design. This study consisted of a series of focus groups (n = 29) and an online survey of adults with POTS (n = 255) focusing on exercise engagement, beliefs, barriers, and facilitators. Qualitative data were analyzed using an iterative inductive-deductive approach, informed by social cognitive theory, which resulted in a conceptual framework and a series of themes. Survey results showed that participants reported a wide range of exercise frequency prior to the onset of POTS symptoms, and overall lower exercise engagement post-POTS. In both survey results and qualitative findings, participants reported believing that exercise is important in managing POTS, but identified barriers to exercise training, including most saliently, their symptom burden. Participants also identified important needs and facilitating factors that could support them in engaging in regular exercise to help manage their condition. These findings shed light on the patient experience of exercise in POTS, which can inform both the tailoring of exercise recommendations and the design of interventions to support exercise engagement specific to the POTS population.

Postural orthostatic tachycardia syndrome (POTS) is a condition defined by symptoms of orthostatic intolerance and a sustained heart rate (HR) increment of ≥ 30 beats per minute (bpm) upon postural change to the upright position in the absence of orthostatic hypotension, defined as a sustained decrease in systolic blood pressure (SBP) of ≥ 20 mmHg or a decrease in diastolic blood pressure (DBP) of ≥ 10 mmHg within 3 min of standing. In children, a sustained HR increment of at least 40 bpm is required for diagnosis of POTS. POTS is a common condition in adults and children suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In daily clinical practice, therapeutic recommendations are rare and evidence is missing. The objective of this review is to present the current knowledge on non-pharmacological and pharmacological approaches in POTS with a special focus on POTS therapy in children and people with ME/CFS. Of 3853 studies, 45 studies were included in the systematic review. Evidence on therapy in POTS is rare and large randomized controlled trials (RCT) on single interventions are needed. Non-pharmacological approaches such as the use of compression garments, physical training, salt supplementation and transdermal vagal nerve stimulation could be possible treatment options in POTS because they are easy to implement as first-line therapeutic measures in clinical practice. For pharmaceuticals, several studies showed significant effects following therapy with ivabradine and β-adrenergic blocking agents. There are single studies which imply that midodrine (hydrochloride) and pyridostigmine seem to have a beneficial effect on hemodynamics in POTS.

Twenty five percent of children who sustain a mild traumatic brain injury (mTBI) or concussion experience persisting post-concussion symptoms (PPCS). The symptoms of PPCS significantly overlap with postural orthostatic tachycardia syndrome (POTS). We aimed to review the literature and investigate the prevalence of POTS in children and adolescents recovering from mTBI. This single centre controlled cross-sectional cohort study recruited children (aged 8-18 years inclusive) diagnosed with mTBI in the emergency department. At 4-6 weeks postinjury, children completed the Active Stand Test. The primary outcome was change in heart rate alongside clinical symptoms consistent with POTS. A total of 113 participants (64 PPCS, 24 mTBI with no clinical symptoms [asymptomatic], and 25 healthy controls) of similar age (mean 13.9 years) and sex (n = 55 [48.7%] male) underwent orthostatic testing. There were no significant group differences in heart rate or blood pressure at baseline, or within 10 minutes of standing. Three (4.8%) symptomatic participants satisfied POTS diagnostic criteria, compared to zero asymptomatic and one (4.2%) control participant. Using the Active Stand Test, a small proportion of children with PPCS satisfied clinical POTS criteria. Although it should be considered in the differential diagnosis, POTS is not common nor overrepresented in PPCS.

BackgroundIndividuals with neurologic impairment, such as brain injury, are more likely to have autonomic dysfunction, including POTS, but often experience a lack of treatment options and access to quality care.ObjectiveExamine the feasibility and outcomes of a group-based multimodal rehabilitation training program.MethodsNineteen females, ages 18-53 (M = 28.6) completed the outpatient training program. The intervention included eight 50-min weekly sessions using an interdisciplinary, multimodal approach, including education, movement, and mindful self-compassion. Participants completed demographic and medical history and assessment for baseline orthostatic intolerance. At pre-training, post-training, and follow-up, participants completed the Modified Fatigue Impact Scale (MFIS), Lower Extremity Functional Scale (LEFS), Rand 36-Item Health Survey 1.0 (RAND-36), Trail Making Test (A and B) (TMT-A, TMT-B), 10-Meter Walk Test (10MWT), and grip strength testing.ResultsAt baseline, participants were significantly below norms in daily function (p < 0.001), grip strength (p ≤ 0.001) gait speed (p < 0.001), fatigue (p < 0.001), and quality of life (p < 0.001). Between pre-training and follow-up, participants showed significant improvement across function in daily life tasks (p < 0.01); grip strength in the dominant (p < 0.01) and non-dominant (p < 0.01) hands; gait speed (p < 0.05); levels of fatigue (p < 0.05); cognitive performance (p < 0.05); and quality of life (p < 0.05).ConclusionIndividuals with POTS face functional challenges that can be significantly and objectively improved through multimodal rehabilitation. There is a need for provider education and further research to optimize care and quality of life for individuals with POTS.

Postural Orthostatic Tachycardia Syndrome (POTS) is a debilitating condition of the autonomic nervous system with no clear referral, diagnosis, and treatment pathways. Patients experience high levels of symptoms and moderate levels of distress. The purpose of this study was to explore biopsychosocial factors associated with distress in those under investigation for POTS, to identify potential targets for intervention. A longitudinal, quantitative survey. Participants (n = 149) completed demographic, psychosocial, and symptom questionnaires prior to a diagnostic POTS clinic visit and 6 months follow-up (n = 98). Correlation and regression analyses were used to identify factors associated with distress at baseline (within one month before diagnostic hospital visit) and at 6 months follow up. At baseline, distress levels were moderate and greater symptom focusing, all-or-nothing and avoidance behaviours, threatening views of the illness, emotional reactivity, cardiac anxiety, POTS symptoms, number of specialists seen, lower social support, and younger age were significantly associated with higher levels of baseline distress. The baseline regression model including all demographic, clinical, and psychosocial factors explained 61.2 % of the variance in distress, with the psychosocial variables collectively explaining 55.6 % of this variance (F = 11.06, p < .001). There was no significant difference between distress levels at baseline and follow-up. Psychosocial variables explained 4.7 % of the variance (F = 0.76, p = .665) in changes in distress scores over 6 months. Baseline distress scores accounted for the vast majority of variance in distress at follow-up. This study identified key novel psychosocial factors that were significantly associated with distress which could be potential targets for intervention. Additional factors such as younger age and a higher number of specialists seen were also associated with higher levels of distress, which merits attention when assessing patients' psychological wellbeing this patient group. Distress levels did not significantly change following the specialist consultation and investigation.

Postural orthostatic tachycardia syndrome (POTS) is a complex disorder with challenging diagnosis and management. This cross-sectional, multi-national, web-based physician chart audit described clinical features and management of POTS, offering insights into disease burden and outcomes before and after the COVID-19 pandemic. Physicians (n = 153), primarily cardiologists (77.1 %), reported data from 599 patients from two cohorts: 1) POTS not triggered by COVID-19 (n = 361) and 2) POTS triggered by COVID-19 (n = 238). Overall, most patients experienced POTS symptoms onset between the ages of 18 and 39 years (33 %), with 13 % presenting symptom onset before 18 years of age. Over 70 % had at least one pre-existing medical condition. Most patients underwent 5-8 tests to define POTS diagnosis. Around 80 % received incorrect diagnoses before POTS confirmation, and 25 % waited over a year for diagnosis. Although some patients showed reduction in symptom severity over time, symptoms were still persistent at last consultation. Non-pharmacological interventions were common in the first treatment line. In subsequent lines, there was an increase in pharmacological treatments, with beta-blockers and ivabradine being the most frequently prescribed medications. Comparative analysis between pre- and post-COVID-19 POTS showed that while POTS patients triggered by COVID-19 were somewhat older and had fewer comorbidities, differences were not clinically meaningful, suggesting similar diagnostic, management and treatment patterns. Regional differences in diagnoses and treatment patterns were observed between US and Europe. This study highlights the challenges faced by POTS patients, while providing insights into the diagnostic and treatment approaches in real-world settings.

Postural orthostatic tachycardia syndrome (POTS) is a complex disorder mainly of orthostatic intolerance, often accompanied by a spectrum of symptoms related to autonomic nervous system dysfunction. Although the diagnostic criteria require an orthostatic challenge test, the associated symptom burden can be broad and is often missed by treating healthcare professionals, resulting in significant diagnostic delay. Treatment of this highly heterogenous condition is nuanced and consists of non-pharmacologic and pharmacologic approaches. Availability of POTS care is limited, with a dearth of medical specialists or general practitioners specialising in autonomic medicine. The complexity of care for those with POTS necessitates a multidisciplinary approach due to the need for extended appointment times and frequent follow-ups to monitor therapeutic response and progress. This should include a primary team consisting of a general practitioner and trained autonomic physicians with specialist nurses, allied health professionals, and any other specialists required to manage the affected systems. This state-of-the-art review aims to cover the key aspects of diagnosing and managing POTS, including special neurological, gastroenterological, psychological, and paediatric considerations. There is an urgent need to provide services that meet the needs of the growing POTS population.

A previous study showed a high prevalence of central sensitization syndrome (CSS) in patients with autonomic symptoms. The prevalence of CSS in postural tachycardia syndrome (POTS), a form of dysautonomia, is unknown. To analyze the prevalence of CSS in POTS. This case-control study included patients with a POTS diagnosis confirmed by autonomic testing at Brigham and Women's Faulkner Hospital between 2022 and 2025. Data were analyzed from April to August 2025. POTS with and without CSS. Central Sensitization Inventory (to assess central sensitization syndrome [CSS]), COMPASS-31 (autonomic symptoms), Neuropathy Total Symptom Score-6 (NTSS-6, sensory symptoms), PROMIS (global health), and autonomic testing (Valsalva maneuver, deep breathing, sudomotor function, and head-up tilt) with skin biopsies. Primary outcome was the central sensitization inventory score with secondary outcomes individual test performances. This study included 305 patients with POTS, of whom 264 (86.6%) met criteria for CSS (mean [SD] age, 33.21 [10.75] years; 30 males [11.4%]; 234 females [88.6%]). Patients with CSS compared with those without CSS had longer duration of symptoms, were more frequently female, exhibited higher rates of anxiety (195 [73.9%] vs 20 [48.8%]; P = .002), depression (168 [63.6% vs 14 [34.1%]; P = .001), fibromyalgia (46 [17.4%] vs 0 [0%]; P = .008), irritable bowel syndrome (IBS, 90 [34.1%] vs 7 [17.1%]; P = .046), headaches (176 [66.7%] vs 12 [29.3 %]; P < .001), treatment with antihistamine medication (136 [51.5%] vs 13 [31.7%]; P = .03), psychiatric medication (163 [61.7%] vs 17 [41.5 %]; P = .02), pain medication (127 [48.1%] vs 8 [19.5%]; P = .001), and gastrointestinal medication (82 [31.1%] vs 5 [12.2 %]; P = .02), and had higher COMPASS-31 scores (51.93 [13.23] vs 31.18 [10.49]; P < .001), NTSS-6 scores (11.32 [4.86] vs 4.44 [3.32]; P < .001), NRS scores (3.26 [2.73] vs 0.54 [1.21]; P < .001), and worse PROMIS scores (20.36 [5.45] vs 27.96 [4.73]; P < .001). Autonomic tests showed lower orthostatic end-tidal carbon dioxide (27.59 [6.39] mm HG vs 29.46 [4.68] mm HG; P = .002) and a greater orthostatic decline in cerebral blood flow velocity (17.08 [8.72] cm/sec vs 13.68 [5.04] cm/sec; P < .001) in the CSS group. Both groups had similar prevalence of autonomic failure (223 [84.5%] vs. 33 [80.5%]; P = .67, mostly mild intensity), and abnormal skin biopsy (43% in both groups). These findings suggest that CSS was common in patients with POTS and may represent a higher-order sequela of cerebrovascular, respiratory, and autonomic dysregulation. This heightened central processing may amplify symptom perception through altered interoceptive signaling. Central sensitization and autonomic impairment may coexist, and management should focus on both conditions.

Orthostatic intolerance (OI) is characterized by the inability to maintain an upright posture without experiencing severe signs and symptoms, including hypotension, palpitations, light-headedness, pallor, fatigue, weakness, dizziness, impaired concentration, tremulousness, and nausea. The majority of patients with myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) exhibit OI, which is the primary factor restricting daily functional capacity. During an upright posture, approximately 800 mL of blood is translocated from the intrathoracic venous compartment to the veins of the buttocks, pelvis, and legs. Under normal conditions, compensatory cardiovascular responses to this orthostatic stress include activation of the muscle pump through calf muscle contraction and a neurogenically mediated increase in heart rate and in systemic vascular resistance. The majority of the symptoms of OI are believed to be cardiovascular and related to reduced cerebral blood flow and excessive activation of the sympathetic nervous system. However, compensatory sympathetic activation is essential for maintaining orthostasis. Many patients have a small left ventricle and associated low cardiac output. In addition, both the renin-aldosterone and antidiuretic hormone systems that regulate circulatory blood volume were downregulated. Postural stability is necessary for maintaining the static balance critical for performing many daily activities. Recently studies have reported that postural instability or disequilibrium, potentially associated with central vestibular dysfunction, should be considered to be involved in the pathogenesis of OI among patients with ME/CFS. Disequilibrium should be recognized as an important cause of OI in those patients.

Long COVID has been an important health concern in children and adolescents, yet factors associated with its development remain incompletely understood. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are widely prescribed for pediatric neuropsychiatric conditions and may influence immune and autonomic pathways involved in postinfectious symptoms. Here we show associations between SSRI/SNRI use and long coronavirus disease (COVID)-related outcomes in a retrospective cohort of 110,955 children and adolescents with pre-existing neuropsychiatric conditions across 37 US health systems participating in the National Institutes of Health Researching COVID to Enhance Recovery consortium. SSRI/SNRI use was not associated with clinician-recorded long COVID diagnosis but showed heterogeneous associations with individual symptoms. Lower risks were observed for some symptoms, including fever, chills and hair loss, whereas higher risks were observed for neurological and systemic outcomes, including postural orthostatic tachycardia syndrome, cognitive dysfunction and fatigue. These findings suggest that antidepressant exposure may be associated with differing post-COVID symptom patterns in youth and warrant further investigation.

We aimed to assess the risk of incident autoimmune and inflammatory conditions during the post-acute period of COVID-19. Descriptive network cohort study. Electronic health records from the UK and Dutch primary care, Norwegian linked health registry, hospital records of specialist centres in Spain, France and Korea and healthcare claims from Estonia and the USA. We followed individuals between September 2020 and the latest available data from day 91 after a SARS-CoV-2 negative test (comparator) or a COVID-19 record (exposed patients, ie assessing patients during the post-acute phase). We further established a reinfection cohort (any further COVID-19 record among the exposed patients). We followed patients until an outcome, end of study period, death, day 365 or an infection (comparator only) or reinfection (exposed patients only). We assessed postural orthostatic tachycardia syndrome (POTS) diagnoses/symptoms, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnoses/symptoms, multi-inflammatory syndrome (MIS) and several autoimmune diseases (rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) and type 1 diabetes mellitus (T1DM)).Meta-analysed crude incidence rate ratios (IRRs) of outcomes after COVID-19 versus negative testing and after reinfection versus a previous COVID-19 record yield the ratios of respective absolute risks of each assessed outcome. We performed subgroup analyses by age, sex and predominant variant periods. We included 2 521 812 individuals with a first COVID-19 record, 4 233 145 with a first negative test and 135 551 with a reinfection. Age and sex were largely comparable between exposure groups with a shorter follow-up for the reinfection cohorts. After COVID-19 compared with test-negative patients and equally after reinfection compared with previous COVID-19 patients, we did not observe increased rates for all outcomes and all subgroup analyses. Counts of MIS and JIA were too small for meta-analyses. In our descriptive meta-analyses of crude IRRs among databases from various countries and settings, we did not observe increased rates of incident POTS, ME/CFS, RA, IBD, SLE and T1DM in COVID-19 versus test-negative or reinfection versus COVID-19 during the first 9 months of the post-acute phase of COVID-19 or reinfection (>90 days postinfection until month 12). Since causal interpretation cannot be made from this study, further causal research is warranted.

On December 10, 2014, the Food and Drug Administration (FDA) licensed the 9-valent human papillomavirus vaccine (9vHPV) for prevention of HPV-related cancers and genital warts. This study aimed to summarize and characterize the first decade of post-licensure surveillance reports of 9vHPV submitted to the Vaccine Adverse Event Reporting System (VAERS). We analyzed VAERS reports following 9vHPV administration in the U.S. during December 2014 through December 2024. Disproportionality analysis was conducted using the reporting odds ratio (ROR) to identify potential safety signals. Reports were categorized by sex, age, seriousness, and clinical outcomes. The VAERS received 23,499 reports following administration of 9vHPV: 46.7% were from females, 25.7% from males, and 27.6% with unreported sex. Overall, 92.5% of reports were nonserious. Syncope, dizziness, loss of consciousness and pallor were most common AEs among nonserious reports. Headache, dizziness, pain and syncope were commonly reported serious AEs. Disproportionality analysis identified six MedDRA PTs that were disproportionately reported following 9vHPV vaccination: anaphylactic shock, postural orthostatic tachycardia syndrome (POTS), dizziness postural, complex regional pain syndrome (CRPS), premature menopause and acute disseminated encephalomyelitis (ADEM). Deaths ( = 57) were rare and most lacked sufficient medical documentation to establish causality. The safety profile of 9vHPV over its first decade of use remains consistent with pre-licensure data, with most AEs being nonserious and self-limiting. Disproportionality analysis identified potential safety signals warranting further investigation but did not confirm causality. Continuous surveillance is necessary to further evaluate these rare events and ensure the ongoing safety of 9vHPV.

The effects of SARS-Cov-2 infection can extend beyond the acute phase of the illness, often described as Long COVID, post-COVID condition (PCC) or Post-acute sequelae of COVID (PASC). Post-acute sequelae (PAS) are also likely to be a problem for a small proportion of children and adolescents following influenza infection. However, there is no comprehensive ongoing data collection in Australian children and adolescents, and global data on both PCC during the SARS-Cov-2 Omicron variant period and PAS following influenza is limited. This study aims to determine the cumulative incidence of PCC in Australian children and adolescents five years after the start of the COVID-19 pandemic. Secondary aims include identifying the cumulative incidence of PAS in children and adolescents following influenza infection. This longitudinal cohort study will recruit children and adolescents aged 0-18 years in South Australia who tested positive for SARS-Cov-2 or influenza in the previous 2 months. Following consent, participants will complete an online baseline survey and then at 3, 6, and 12 months post-infection. The survey has been adapted from the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) Paediatric COVID-19 follow-up survey. The survey includes validated assessment tools such as the Pediatric Quality of Life Inventory (PedsQL), Multidimensional Fatigue Scale, and the Malmö Postural Orthostatic Tachycardia Syndrome (POTS) Score questionnaire. PCC following COVID-19 and PAS following influenza infection will be identified according to an adapted World Health Organization definition of PCC in children and adolescents. This study addresses gaps in understanding PCC and PAS following influenza in children and adolescents during Omicron circulation. Whilst it is no longer feasible to prospectively compare post-acute sequelae in children and adolescents who have never had COVID-19, this design allows a comparison with another common viral infection, influenza, informing clinical management of children post-infection.

Background and objective Unexplained syncope remains a frequent and challenging clinical problem, even after guideline-directed cardiovascular and neurological evaluation. In a substantial proportion of patients, syncope remains without an identified etiology after conventional investigations, suggesting alternative underlying mechanisms. Autonomic nervous system (ANS) dysfunction plays a central role in cardiovascular regulation and has been increasingly recognized as a key contributor to unexplained syncope. ANS testing allows objective evaluation of cardiovascular autonomic reflexes, including sympathetic and parasympathetic responses to orthostatic and physiological stressors. The objective of this study was to assess autonomic profiles using standardized ANS testing in patients referred for unexplained syncope and to characterize dysautonomic patterns that may contribute to syncope mechanisms. Methods We conducted a retrospective mono-centric study including 90 consecutive adult patients referred to a tertiary autonomic unit for syncope remaining without an identified etiology after conventional evaluation between January 2024 and June 2025. All patients underwent a standardized ANS testing battery, including an active standing (orthostatic) test, a deep-breathing test, an isometric handgrip test, and a mental stress test. Demographic data, cardiovascular risk factors, clinical presentation, and ANS test results were systematically collected and analyzed. Results ANS testing identified autonomic abnormalities considered clinically relevant in a high proportion of patients with unexplained syncope despite routine conventional investigations. The most frequent findings included exaggerated vagal responses, orthostatic intolerance syndromes such as postural orthostatic tachycardia syndrome, sympathetic alpha-adrenergic dysfunction leading to orthostatic hypotension, and mixed autonomic profiles. Overlapping autonomic phenotypes were frequently observed within the same patient, underscoring the complexity of dysautonomic syncope. Conclusion ANS testing provides a high diagnostic yield in patients with syncope remaining without an identified etiology after standard evaluation by revealing clinically relevant autonomic dysregulation. Integration of ANS testing as a second-line diagnostic approach may improve etiological classification and support individualized management strategies in selected patients.

Postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID are heterogeneous disorders with overlapping complex, multi-factorial and multi-systemic pathophysiology. POTS and ME/CFS are the most common phenotypes of Long COVID that can lead to significant disability and functional impairment. The exact pathophysiologic mechanisms of these disorders alone or in combination are still being investigated, but important mechanistic factors have been identified, such as autonomic dysfunction, immune dysregulation, autoimmunity, mitochondrial dysfunction, cerebral hypoperfusion, and neuroinflammation. To this end, we believe that these conditions should be viewed as neuroimmune disorders and should be included in the field of neuroimmunology, with its educational curriculum, training, and clinical care pathways. Including these disorders as part of neuroimmunology subspecialty is the key to advancing the science and clinical care of this underserved patient population with these complex and disabling conditions.

Postural orthostatic tachycardia syndrome (POTS) is defined by chronic orthostatic intolerance accompanied by an excessive increment in sinus heart rate on standing in the absence of significant orthostatic hypotension. Contemporary reviews and consensus statements appropriately frame POTS as involving autonomic regulation. Yet the bedside phenotype most often observed-marked tachycardia with preserved blood pressure-also supports a hemodynamic interpretation: an intact baroreflex driving tachycardia to defend cardiac output and cerebral perfusion when effective stroke volume or venous return is reduced. This narrative, hypothesis-driven review argues that the umbrella label 'dysautonomia' is frequently applied imprecisely in POTS and is often interpreted (by clinicians and patients) as autonomic failure. In many patients, the dominant physiology is not autonomic failure but compensatory activation in response to orthostatic stressors such as low central blood volume, venous pooling, impaired vasoconstriction, or deconditioning. When the label is over-interpreted, management can drift toward reflexive heart-rate suppression rather than mechanism-directed evaluation and treatment of the orthostatic stressor. We propose a pragmatic, cardiology-facing framework that (1) distinguishes compensatory orthostatic tachycardia from primary autonomic failure (neurogenic orthostatic hypotension), and (2) prioritizes mechanistic phenotyping within POTS (low-preload/pooling dominant, neuropathic, hyperadrenergic, immune-associated, and secondary structural/CSF-pressure contributors). This reframing does not minimize the severity of POTS; rather, it supports clearer counseling and more targeted therapy by treating tachycardia as a signal of orthostatic stress and asking what is driving it.